Azithromycin Protects against Zika virus Infection by Upregulating virus-induced Type I and III Interferon Responses

Chunfeng Li; Shulong Zu; Yong-Qiang Deng; Dapei Li; Kislay Parvatiyar; Natalie Quanquin; Jingzhe Shang; Nina Sun; Jiaqi Su; Zhenyang Liu; Min Wang; Saba R Aliyari; Xiao-Feng Li; Aiping Wu; Feng Ma; Yi Shi; Karin Nielsevn-Saines; Jae U Jung; Frank Xiao-Feng Qin; Cheng-Feng Qin; Genhong Cheng

doi:10.1128/AAC.00394-19

Azithromycin Protects against Zika virus Infection by Upregulating virus-induced Type I and III Interferon Responses

Antimicrob Agents Chemother. 2019 Sep 9;63(12):e00394-19. doi: 10.1128/AAC.00394-19. Epub 2019 Sep 16.

Authors

Chunfeng Li^{1

2

3}, Shulong Zu^{4

5}, Yong-Qiang Deng², Dapei Li⁶, Kislay Parvatiyar⁷, Natalie Quanquin⁷, Jingzhe Shang⁶, Nina Sun^{4

5}, Jiaqi Su^{5

8}, Zhenyang Liu^{5

8}, Min Wang^{5

8}, Saba R Aliyari⁷, Xiao-Feng Li², Aiping Wu⁶, Feng Ma⁶, Yi Shi⁸, Karin Nielsevn-Saines⁹, Jae U Jung¹⁰, Frank Xiao-Feng Qin⁶, Cheng-Feng Qin¹¹, Genhong Cheng¹²

Affiliations

¹ Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China gcheng@mednet.ucla.edu qincf@bmi.ac.cn chunfeng@stanford.edu.
² Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
³ Institute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
⁴ CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
⁵ University of Chinese Academy of Sciences, Beijing 100049, China.
⁶ Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China.
⁷ Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
⁸ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁹ Division of Pediatric Infectious Diseases, David Geffen School of Medicine, UCLA, Marion Davies Children's Health Center, Los Angeles, California, USA.
¹⁰ Department of Molecular Microbiology and Immunology and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Zilkha Neurogenetic Institute, Los Angeles, California, USA.
¹¹ Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China gcheng@mednet.ucla.edu qincf@bmi.ac.cn chunfeng@stanford.edu.
¹² Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA. gcheng@mednet.ucla.edu qincf@bmi.ac.cn chunfeng@stanford.edu.

Abstract

Azithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Herein, we report that AZM effectively suppresses ZIKV infection in vitro by targeting a late stage in the viral life cycle. Besides that, AZM upregulates the expression of host type I and III interferons and several of their downstream interferon-stimulated genes (ISGs) in response to ZIKV infection. In particular, we found that AZM upregulates the expression of MDA5 and RIG-I, pathogen recognition receptors (PRRs) induced by ZIKV infection, and increases the levels of phosphorylated TBK1 and IRF3. Interestingly, AZM treatment upregulates phosphorylation of TBK1, without inducing phosphorylation of IRF3 by itself. These findings highlight the potential use of AZM as a broad antiviral agent to combat viral infection and prevent ZIKV associated devastating clinical outcomes, such as congenital microcephaly.

Abstract

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